Cells in many tissues display polarity within the plane of the tissue. This is often called planar cell polarity (PCP) and this project focuses on the genetic, cell biological and molecular basis for PCP. Previous work funded by this grant discovered a genetic regulatory pathway for PCP in the Drosophila model system and it has been found to be conserved in vertebrates including humans. Mutations in PCP genes have been linked to a failure in neural closure, polycystic kidney disease, hearing and balance problems and heart and lung developmental defects. The pathway consists of a regulatory hierarchy, with the fz-like PCP genes being upstream of the planar polarity effector (PPE) genes which are in turn upstream of the mwh gene. The proteins that are encoded by pathway genes all accumulate asymmetrically in epithelial cells and this is thought to be essential to their function. A major goal of the application is to understand how polarity information is passed on from one group to the next in the hierarchy. A variety of genetic and biochemical experiments are designed to test models about how this is accomplished.
The second aim of the proposal is to determine the stoichiometry of proteins in the PCP complexes. An innovative microscopy approach will be taken.
The final aim i s to determine where in the PCP hierarchy a number of newly identified PCP genes function.

Public Health Relevance

The conserved PCP regulatory pathway is essential for the proper morphogenesis of a wide variety of cells, tissues and organs including the epidermis, stereocilia of the inner ear, muscle, bone, heart, lung, kidney and embryonic tissues undergoing cellular movements. Mutations of genes in this pathway have been found to be associated with a failure of neural tube closure, polycystic kidney disease, cancer and hearing and balance problems. This project is focused on understanding the function of several genes in this pathway, which could lead to potential treatments for these health problems.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
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Development - 2 Study Section (DEV2)
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Hoodbhoy, Tanya
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University of Virginia
Schools of Arts and Sciences
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Wang, Ying; Naturale, Victor F; Adler, Paul N (2017) Planar Cell Polarity Effector Fritz Interacts with Dishevelled and Has Multiple Functions in Regulating PCP. G3 (Bethesda) 7:1323-1337
Sobala, Lukasz F; Adler, Paul N (2016) The Gene Expression Program for the Formation of Wing Cuticle in Drosophila. PLoS Genet 12:e1006100
Lu, Qiuheng; Adler, Paul N (2015) The diaphanous gene of Drosophila interacts antagonistically with multiple wing hairs and plays a key role in wing hair morphogenesis. PLoS One 10:e0115623
Sobala, Lukasz F; Wang, Ying; Adler, Paul N (2015) ChtVis-Tomato, a genetic reporter for in vivo visualization of chitin deposition in Drosophila. Development 142:3974-81
Lu, Qiuheng; Schafer, Dorothy A; Adler, Paul N (2015) The Drosophila planar polarity gene multiple wing hairs directly regulates the actin cytoskeleton. Development 142:2478-86
Wang, Ying; Yan, Jie; Lee, Haeryun et al. (2014) The proteins encoded by the Drosophila Planar Polarity Effector genes inturned, fuzzy and fritz interact physically and can re-pattern the accumulation of ""upstream"" Planar Cell Polarity proteins. Dev Biol 394:156-69
Fagan, Jeremy K; Dollar, Gretchen; Lu, Qiuheng et al. (2014) Combover/CG10732, a novel PCP effector for Drosophila wing hair formation. PLoS One 9:e107311
Adler, Paul N; Sobala, Lukasz F; Thom, Desean et al. (2013) dusky-like is required to maintain the integrity and planar cell polarity of hairs during the development of the Drosophila wing. Dev Biol 379:76-91
Adler, Paul N (2012) The frizzled/stan pathway and planar cell polarity in the Drosophila wing. Curr Top Dev Biol 101:1-31
Nagaraj, Ranganayaki; Adler, Paul N (2012) Dusky-like functions as a Rab11 effector for the deposition of cuticle during Drosophila bristle development. Development 139:906-16

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